What epidemiology has told us about risk factors and aetiopathogenesis in rheumatic diseases

Table 1 Risk factors for the major rheumatic diseases over the past 10 years

Disease	Host/Environmental risk factor	Gene
Rheumatoid arthritis	Diet (caffeine and Mediterranean diet)	PTPN22
	Smoking	PADI4
	Hormones	CTLA4
		FCRL3
		MHC2A
		HLA DRB1
Juvenile idiopathic arthritis		Macrophage inhibitory factor (MIF)
		PTPN22
		NRAMP1
		IL-6
Psoriatic arthritis	Rubella vaccination	CARD15
	Injury requiring medical consultation	MICA
	Recurrent oral ulcers	TNF
	Moving house	IL
	Corticosteroids
	Pregnancy
Ankylosing spondylitis		ARTS1
		IL-23R
		IL-1 gene cluster
		Cytochrome P450 2D6 (CYP2D6) gene
Systemic lupus erythematosus	Breast-feeding	MHC
	Early natural menopause	ITGAM
	Lipstick	IRF5
		BLK
		STAT4
		PTPN22
		FCGR2A
Scleroderma	Exposure to silica or organic solvents	Familial risk
		HLA-DQA1
		Fibrillin-1 SNP haplotypes
		TGF-β
		CTGF
		Foetal microchimerism
Osteoarthritis	Obesity/Body mass index	IL-1 gene cluster
	Physical activity	Frizzled-related protein-3 (FRZB) gene
	Grip strength	Matrilin-3 gene
	Previous injury	IL-4 receptor
		Metalloproteinase gene ADAM12
		Asporin (ASPN) gene
		Estrogen receptor
Gout	High purine diet	TNF-α promoter
	Dairy products
	Hypertension
	Pharmacologic agents
Fibromyalgia and chronic widespread pain	Physical trauma	Serotonin transporter gene
	Somatisation	Familial risk
	Health-seeking behaviour	COMT
	Poor sleep

ADAM12, a disintegrin and metalloproteinase domain 12; ARTS1, type 1 tumor necrosis factor receptor shedding aminopeptidase regulator; BLK, B lymphoid tyrosine kinase; CARD15, caspase recruitment domain 15; COMT, catechol-O-methyltransferase; CTGF, connective tissue growth factor; CTLA4, cytotoxic T lymphocyte-associated antigen-4; FCGR2A, Fc fragment of IgG, low-affinity IIA, receptor (CD32); FCRL3, Fc-receptor like-3; IL, interleukin; IRF5, interferon regulatory factor 5; ITGAM, integrin, alpha M; MHC, major histocompatibility complex; MHC2A, major histocompatibility complex 2A; MICA, class I major histocompatibility complex chain-related gene A; NRAMP1, natural-resistance-associated macrophage protein 1; PADI4, peptidyl arginine; PTPN22, protein tyrosine phosphatase; SNP, single-nucleotide polymorphism; STAT4, signal transducer and activator of transcription 4; TGF-β, transforming growth factor-beta; TNF, tumour necrosis factor.

ISSN: 1478-6362